RCMI-CCRHD Research Projects 2017–2022 “Upstream Regulation and Downstream Effectors of c-MYC in Ovarian Cancer”

Research Areas

  • Nanoparticle formulations for delivery of RNA molecules for cancer treatment.
  • Expression profiles and targeting of microRNAs in cancer.
  • Design of small molecule inhibitors against cancer-related proteins.

Scientific Achievements

  • Identify key molecular players responsible of the cisplatin resistance in ovarian cancer cells.
  • Demonstrate that microRNA-18a-5p suppresses tumor growth via targeting matrix metalloproteinase-3 in cisplatin- resistant ovarian cancer.
  • Demonstrate that upregulation of the long noncoding RNA CASC10 promotes cisplatin resistance in high-grade serous ovarian cancer.
  • Develop a small-interference RNA (siRNA)-liposomal formulation targeting CASC10 to the treatment of cisplatin resistant ovarian cancer (US Provisional Patent Application 63/343,974 / Novel Targets Against Ovarian Cancer).

Funding

RCMI Funding:

  • NIH/NIMHD U54MD007600

Other funding obtained with RCMI support: R16 (SURE) NIGMS: 1R16GM145558; Unraveling the Role of MMP3 in the Cisplatin Resistance of Ovarian Cancer.

Scientific Advance

Upregulation of MMP3 Promotes Cisplatin Resistance in Ovarian Cancer
Published in International Journal of Molecular Sciences, Volume 26, 2025, PMCID: PMC12071843.
This study investigates why some ovarian cancer cells stop responding to cisplatin, a commonly used chemotherapy drug, by focusing on the role of a protein called MMP3. They found that cisplatin-resistant ovarian cancer cells have much higher levels of MMP3 than cisplatin-sensitive ones. When they reduce MMP3 levels using molecular tools, the resistant cells become less able to survive, grow, or invade, especially when combined with cisplatin treatment. They also looked at the changes in many genes and proteins when MMP3 is reduced, showing that many pathways related to cell cycle control, death (apoptosis), metabolism, stress responses, and the structure around cells are affected. In mouse models, targeting MMP3 together with cisplatin led to slower tumor growth compared to treatments alone. The research suggests that MMP3 contributes to multiple processes that allow cancer cells to resist treatment, and that targeting MMP3 may improve response to cisplatin in ovarian cancer.
U54-MD007600/NIMHD NIH HHS/United States, 5R16GM145558/NIGMS NIH HHS/United States, 5R25GM061151-20/NIGMS NIH HHS/United States, R25 GM061838/NIGMS NIH HHS/United States, P20GM103475/NIMHD NIH HHS/United States, U54NS043011/NIMHD NIH HHS/United States
Toggle Navigation